Thyrotropin biosynthesis and carbohydrate processing has been studied under various physiologic conditions and in the presence of various carbohydrate processing inhibitors. Deoxynojirimycin, which inhibits glucosidase action and leads to accumulation of glucosylated precursors, caused inhibition of thyrotropin secretion but no effects on the secretion of nonglycoprotein hormones. Thyroid hormone and thyrotropin-releasing hormone (TRH) caused differential effects on thyrotropin apoprotein and carbohydrate synthesis and secretion. TSH carbohydrate structure is heterogeneous, and thyrotropin-releasing hormone caused a specific increase in synthesis and secretion of biantennary complex forms. Patients with invasive thyrotropin-secreting pituitary tumors may secrete TSH with more branched carbohydrate structure. The carbohydrate structure of TSH changes during neonatal development and is altered by paraventricular nuclear lesions in rats causing hypothalamic hypothyroidism. The effects of TRH on TSH carbohydrate structure are specific and not induced by non-specific secretagogues such as potassium.